2v3s | pdb_00002v3s

Structural insights into the recognition of substrates and activators by the OSR1 kinase

spinqualitylabelsall models 2v3s, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2v3s is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.7Å Ligands: ACT Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function OXSR1_HUMAN Regulates downstream kinases in response to environmental stress. May also have a function in regulating the actin cytoskeleton. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The oxidative-stress-responsive kinase 1 (OSR1) and the STE20/SPS1-related proline/alanine-rich kinase (SPAK) are key enzymes in a signalling cascade regulating the activity of Na(+)/K(+)/2Cl(-) co-transporters (NKCCs) in response to osmotic stress. Both kinases have a conserved carboxy-terminal (CCT) domain, which recognizes a unique peptide (Arg-Phe-Xaa-Val) motif present in OSR1- and SPAK-activating kinases (with-no-lysine kinase 1 (WNK1) and WNK4) as well as its substrates (NKCC1 and NKCC2). Here, we describe the structural basis of this recognition event as shown by the crystal structure of the CCT domain of OSR1 in complex with a peptide containing this motif, derived from WNK4. The CCT domain forms a novel protein fold that interacts with the Arg-Phe-Xaa-Val motif through a surface-exposed groove. An intricate web of interactions is observed between the CCT domain and an Arg-Phe-Xaa-Val motif-containing peptide derived from WNK4. Mutational analysis shows that these interactions are required for the CCT domain to bind to WNK1 and NKCC1. The CCT domain structure also shows how phosphorylation of a Ser/Thr residue preceding the Arg-Phe-Xaa-Val motif results in a steric clash, promoting its dissociation from the CCT domain. These results provide the first molecular insight into the mechanism by which the SPAK and OSR1 kinases specifically recognize their upstream activators and downstream substrates. Structural insights into the recognition of substrates and activators by the OSR1 kinase.,Villa F, Goebel J, Rafiqi FH, Deak M, Thastrup J, Alessi DR, van Aalten DM EMBO Rep. 2007 Sep;8(9):839-45. Epub 2007 Aug 17. PMID:17721439 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Serine/threonine protein kinase 3D structures

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